CD95/Fas protects triple negative breast cancer from anti-tumor activity of NK cells
Abdul S. Qadir,
Jean Philippe Guégan,
Christophe Ginestier,
Assia Chaibi,
Alban Bessede,
Emmanuelle Charafe-Jauffret,
Manon Macario,
Vincent Lavoué,
Thibault de la Motte Rouge,
Calvin Law,
Jacob Vilker,
Hongbin Wang,
Emily Stroup,
Matthew J. Schipma,
Bryan Bridgeman,
Andrea E. Murmann,
Zhe Ji,
Patrick Legembre,
Marcus E. Peter
Affiliations
Abdul S. Qadir
Division Hematology/Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Jean Philippe Guégan
Explicyte, Cours de l’Argonne, 33000 Bordeaux, France
Christophe Ginestier
CRCM, Inserm, CNRS, Institut Paoli-Calmettes, Aix-Marseille Univ, Epithelial Stem Cells and Cancer Lab, Equipe labellisée LIGUE contre le cancer, Marseille, France
Assia Chaibi
Explicyte, Cours de l’Argonne, 33000 Bordeaux, France
Alban Bessede
Explicyte, Cours de l’Argonne, 33000 Bordeaux, France
Emmanuelle Charafe-Jauffret
CRCM, Inserm, CNRS, Institut Paoli-Calmettes, Aix-Marseille Univ, Epithelial Stem Cells and Cancer Lab, Equipe labellisée LIGUE contre le cancer, Marseille, France
Manon Macario
CRCM, Inserm, CNRS, Institut Paoli-Calmettes, Aix-Marseille Univ, Epithelial Stem Cells and Cancer Lab, Equipe labellisée LIGUE contre le cancer, Marseille, France
Vincent Lavoué
Department of Gynecology, University Hospital of Rennes, Rennes, France
Thibault de la Motte Rouge
Centre Eugène Marquis, Rennes, France
Calvin Law
Division Hematology/Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Jacob Vilker
Division Hematology/Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Hongbin Wang
Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Emily Stroup
Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Matthew J. Schipma
Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Bryan Bridgeman
Division Hematology/Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Andrea E. Murmann
Division Hematology/Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Zhe Ji
Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA
Division Hematology/Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Corresponding author
Summary: The apoptosis inducing receptor CD95/Fas has multiple tumorigenic activities. In different genetically engineered mouse models tumor-expressed CD95 was shown to be critical for cell growth. Using a combination of immune-deficient and immune-competent mouse models, we now establish that loss of CD95 in metastatic triple negative breast cancer (TNBC) cells prevents tumor growth by modulating the immune landscape. CD95-deficient, but not wild-type, tumors barely grow in an immune-competent environment and show an increase in immune infiltrates into the tumor. This growth reduction is caused by infiltrating NK cells and does not involve T cells or macrophages. In contrast, in immune compromised mice CD95 k.o. cells are not growth inhibited, but they fail to form metastases. In summary, we demonstrate that in addition to its tumor and metastasis promoting activities, CD95 expression by tumor cells can exert immune suppressive activities on NK cells, providing a new target for immune therapy.
